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Breast Imaging |
1 From the Departments of Radiology (S.G.L., S.G.O., M.D.S.), Biostatistics and Epidemiology (M.E.P.), Radiation Oncology (L.J.S.), and Surgery (B.J.C.), Hospital of the University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104; Department of Radiology, Crozer-Chester Medical Center, Upland, Pa (I.J.W.); and Marques y Perez Radiologists, San Juan, PR (E.C.J.). Received February 5, 2002; revision requested April 10; revision received July 8; accepted August 15. Address correspondence to S.G.L. (e-mail: lees@rad.upenn.edu).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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MATERIALS AND METHODS: Between January 1999 and July 2001, 182 patients with newly diagnosed breast cancer (after either core or excisional biopsy with positive or close margins of resection) underwent bilateral contrast material–enhanced MR imaging at 1.5 T with a dedicated bilateral breast multicoil array. The contralateral breast was imaged for cancer screening. Family history of breast cancer, index cancer histology, breast density, and age at diagnosis of first breast cancer were assessed as potential risk factors for synchronous contralateral breast cancer.
RESULTS: Fifteen patients (8.2%) had a suspicious enhancing lesion depicted in the contralateral breast. Seven patients (3.8%) had malignant results: ductal carcinoma in situ (DCIS) in four, invasive ductal carcinoma with DCIS in two, and invasive ductal carcinoma in one. Eight patients (4.4%) had benign results: fibrocystic changes in four, atypical ductal hyperplasia in two, atypical lobular hyperplasia and focal lobular carcinoma in situ in one, and ductal hyperplasia in one. Six patients with negative MR findings underwent prophylactic mastectomy; no malignancy was found. No significant differences were noted among patients with true-positive (n = 7), false-positive (n = 8), or negative (n = 167) MR findings with regard to family history of breast cancer (P < .27), index cancer histology (P < .19), breast density (P < .34), or age at diagnosis of first breast cancer (P < .10).
CONCLUSION: The preliminary results demonstrate the feasibility of using MR imaging of the breast in a screening role, specifically to evaluate the contralateral breast in patients with newly diagnosed breast cancer to detect mammographically and clinically occult synchronous breast cancer.
© RSNA, 2003
Index terms: Breast, MR, 00.121411, 00.121412, 00.121415, 00.12143 • Breast neoplasms, diagnosis, 00.30 • Magnetic resonance (MR), utilization, 00.30
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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There are multiple reports in the literature demonstrating the increased sensitivity of magnetic resonance (MR) imaging for the detection of breast cancer compared with that of conventional methods, with reported sensitivity of MR imaging for detection of invasive breast cancer approaching 100% (5–8). Most of these studies evaluated MR imaging in the diagnostic setting, specifically in patients suspected or known to have breast cancer. How MR imaging will perform in a screening setting is not clear. There are a few reports demonstrating the potential of MR imaging for breast cancer, specifically in patients at increased risk for the development of breast cancer. The purpose of this study was to investigate the role of screening MR imaging in the detection of synchronous contralateral breast cancer in patients with newly diagnosed breast cancer.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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Imaging and Biopsy
MR imaging was performed with a 1.5-T system (Signa; GE Medical Systems, Milwaukee, Wis) equipped with a high-performance gradient system. All examinations were performed with a home-built prototypic bilateral phased-array multicoil, with the patient imaged in a prone position with each breast compressed gently between medial and lateral plates (10). All examinations included sagittal T1-weighted spin-echo (500/14 [repetition time msec/echo time msec]); T2-weighted, fat-suppressed, fast spin-echo (4,000/120); and T1-weighted, fat-suppressed, spoiled gradient-echo sequences before and after injection of contrast material. The contrast-enhanced sequence was a three-dimensional, dynamic, fat-suppressed, fast spoiled gradient-echo sequence (minimum repetition time msec/minimum echo time msec, 30°-90° flip angle, 28 sections obtained in a minimum of 1 minute 27 seconds and in a maximum of 2 minutes 52 seconds, small field of view [160–180 mm], large matrix [512 x 256], and thin sections [2–3 mm, with no intersection gap]). Fat suppression was obtained by using a spectrally fat-selective inversion pulse. Contrast material (0.1 mmol per kilogram of body weight gadopentetate dimeglumine [Magnevist; Berlex, Wayne, NJ]) was injected intravenously during approximately 10 seconds and was followed by a normal saline flush; image acquisition was begun immediately. Postprocessing image subtraction was performed with a workstation. For patients with a suspicious lesion detected only with MR imaging, MR imaging–guided wire localization or core biopsy was performed. The details of this procedure have been previously described (11).
Image Interpretation
The MR images were read prospectively by one of two radiologists (S.G.O., M.D.S.) experienced in interpreting breast MR imaging studies. The images were read with the knowledge that the patient had newly diagnosed breast cancer. Prior mammographic or ultrasonographic (US) studies or reports were available for review at the time of MR image interpretation. Enhancement of breast lesions was assessed qualitatively relative to the signal intensity of the background glandular tissue on the first postcontrast images obtained at 2 minutes 30 seconds. A lesion was considered suspicious if it enhanced after contrast material administration and had partially irregular or ill-defined margins, if it enhanced peripherally, or if it enhanced in a linear or branching pattern suggestive of ductal enhancement. An enhancing lesion was considered to be benign if it had circumscribed margins or if it had minimal enhancement after contrast material administration. If multiple suspicious enhancing lesions were identified, the dominant lesions would be noted and be recommended for biopsy. Scattered punctate (1–3-mm) foci of enhancement or patchy diffuse enhancement of the fibroglandular tissue with no associated architectural distortion was considered a benign finding. If a suspicious lesion was identified on MR images, any prior mammograms or sonograms were reviewed and additional mammographic or US imaging was performed at the discretion of the reviewing radiologist for prebiopsy planning.
Specimen Evaluation
In the pathology department, the edges of all breast specimens were marked with india ink. In cases in which the lesion was localized with MR imaging guidance or with mammographic guidance, the area of concern was marked with a different color of india ink. A diagram delineating the relationship of the lesion to the hookwire (for MR imaging–guided localizations) or a radiograph of the specimen (for mammography-guided localizations) accompanied all specimens to the pathology department. The specimen was then serially sectioned and submitted in its entirety for microscopic examination. The size of any lesion was measured.
Statistics
Statistical analyses were performed by using exact CIs and tests implemented with StatXact version 4 (Cytel Software, Cambridge, Mass). Exact methods avoid large sample statistical approximations and are appropriate when samples are small. A 
2 test of independence or the Fisher-Freeman-Halton test was used to test for associations between descriptive variables (family history of cancer, index cancer histology, or breast density) and outcome (negative MR finding, false-positive MR finding, or true-positive MR finding). A Kruskal-Wallis test was performed to determine if there were differences in age among patients with negative MR findings, false-positive MR findings, or true-positive MR findings. A P value of less than .05 was considered to indicate a statistically significant difference.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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Seven (3.8%) of the 182 patients had malignant histopathologic results among the 15 suspicious lesions (Table 1). Four of the seven malignant lesions were identified only on MR images: invasive ductal carcinoma (0.3 cm) and ductal carcinoma in situ ([DCIS] 2.1 cm) in one case, and DCIS (focus in two, 0.2 cm in one) in three cases. One patient with a suspicious enhancing lesion on MR images had a corresponding hypoechoic mass on follow-up sonograms (Fig 1). Fine-needle aspiration with US guidance demonstrated a suspicious tumor, which was confirmed as DCIS at the patient’s elective mastectomy. Another suspicious lesion on MR images corresponded to a group of calcifications with an associated mass at follow-up diagnostic mammography (Fig 2). Findings of excisional biopsy after mammography-guided wire localization showed invasive ductal carcinoma with focally present DCIS outside the lesion. In another patient, a suspicious, enhancing lesion corresponded to a subtle hypoechoic lesion on sonograms (Fig 3). As the lesion was better visualized at MR imaging, the patient underwent MR imaging–guided core-needle biopsy, which revealed well-differentiated infiltrative ductal carcinoma. Excisional biopsy revealed benign findings in eight (4.4%) of the 182 patients (Table 1).
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Eight (4.4%) of the 182 patients had false-positive MR studies that led to biopsy among the 15 suspicious lesions. In six patients, excisional biopsy was performed after MR imaging–guided wire localization (Fig 4). In one patient, corresponding lesions were identified on sonograms, and the patient underwent US-guided core-needle biopsy (Fig 5). However, the results were discordant. Instead of excisional biopsy, the patient elected to have a simple mastectomy as part of a bilateral mastectomy procedure. The last patient elected to have a simple mastectomy as part of a bilateral mastectomy procedure.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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There are many examples of diagnostic MR imaging depicting mammographically and clinically occult breast cancers (5,7,14). In most of these studies, MR imaging was evaluated in the diagnostic setting, most often in patients suspected of having or with newly diagnosed breast cancer. The potential of diagnostic MR imaging for increased sensitivity for the detection of breast cancer compared with that of conventional methods has stimulated extensive interest in using MR imaging for breast cancer screening.
Clinical investigation of MR imaging for breast cancer screening is ongoing. Most of the current studies involve patients at increased risk for the development of breast cancer. Clinical histories have included a personal history of breast cancer, a known or suspected carrier of one of the breast cancer genes BRCA1 or BRCA2, a history of atypical ductal hyperplasia or lobular carcinoma in situ, or a history of radiation therapy to the chest or the mediastinum.
In our study, we evaluated the contralateral breast in patients with newly diagnosed breast cancer. The frequency of MR imaging-detected contralateral breast cancer in our series was 3.8% (seven of 182 patients). The seven malignancies detected in the contralateral breast were both mammographically and clinically occult. The rate of synchronous cancer found in our series is lower than that previously reported by Fischer et al (15) (4.5%, 15 of 336 patients), Slanetz et al (16) (9.5%, four of 42 patients), and Rieber et al (17) (8.8%, three of 34 patients). Possible explanations for the lower frequency of synchronous cancer found in our series compared with that of these other series include relatively small numbers of patients examined and potential differences in patient populations (including the percentage of patients at increased risk).
Although our results along with those of other investigators demonstrate the ability of MR imaging to depict breast cancer that is occult to conventional imaging methods, as well as occult to physical examination, our result also highlights one ongoing limitation of MR imaging of the breast, that of low specificity. The limited specificity of MR imaging of the breast has been reported by many investigators. There is an overlap in appearance of enhancing breast cancer with that of enhancing benign lesions. In our series, there were eight (4.4%) false-positive studies, which led to biopsy in all eight cases, including mastectomies in two patients. Additional surgical procedures could be avoided if MR imaging–guided core biopsy was readily available. MR imaging-compatible core biopsy devices are currently being developed, but are not yet widely commercially available.
It will not likely be realistic or feasible to screen the contralateral breast in all patients with newly diagnosed breast cancer. Clinical investigation into identifying those patients who are at greatest risk for synchronous bilateral breast cancer, and who might benefit most from screening with MR imaging, is ongoing. Risk factors historically associated with contralateral breast cancer include young age at time of diagnosis of the first breast cancer, family history of breast cancer, and presence of invasive lobular carcinoma (4,18). In our series, age at time of diagnosis of the first breast cancer, family history of breast cancer, and index cancer histology were evaluated. No significant differences were noted in the occurrence of these risk factors when our patient population was subdivided into three subgroups: true-positive, false-positive, and negative MR findings. Breast density also was evaluated, and no significant difference was noted in breast density distribution among the three subgroups. Our inability to identify one or more risk factors is likely due to the small number of patients with contralateral malignancy found in our series thus far. A larger study, ideally a multiinstitutional study, may help to identify these risk factors.
There are limitations of our study. One limitation is potential biases resulting from patient selection. Entrance criteria for this study included patients with newly diagnosed breast cancer found at core biopsy or excisional biopsy (positive or close margins of resection) who were believed to be eligible for breast-conservation therapy. Patients with newly diagnosed breast cancer who had more extensive disease and were not eligible for breast-conservation therapy were excluded. Thus, the study group comprised patients with smaller tumors. These entry criteria may affect the likelihood of identifying cancers in the contralateral breast. Owing to constraints in funding, as well as in MR imaging availability, not all eligible patients could be enrolled. Although we tried to keep enrollment random by allowing availability entirely open to all patients, the scheduling of patients was at the discretion of the surgeon.
A second limitation of this study is that the true sensitivity and specificity of screening MR imaging are unknown. Six patients with negative MR imaging findings underwent prophylactic mastectomy. No malignancy was found in all six patients. However, follow-up of those patients who did not undergo mastectomy is needed to determine if there were any false-negative cases.
The clinical importance of contralateral breast cancer, particularly DCIS, detected only with MR imaging is not known. Which foci of DCIS or invasive carcinoma detected on MR images in the contralateral breast will progress to become clinically important? Which of these cancers would likely be adequately treated with chemotherapy that was given to treat the ipsilateral breast? Will patients who are treated for contralateral breast cancer detected only with MR imaging have a better overall survival than patients who do not undergo MR imaging and are treated for contralateral breast cancer detected with either mammography or clinical examination? Further investigative studies, including prospective clinical trials, need to be performed to address these questions.
Our preliminary results along with those of other investigators have demonstrated the feasibility of using MR imaging of the breast in a screening role, specifically to evaluate the contralateral breast in patients with newly diagnosed breast cancer. MR imaging is expensive, however, and it will likely not be realistic that all patients with newly diagnosed breast cancer will undergo MR imaging screening of the contralateral breast. Cost-effectiveness analysis needs to be performed to determine if the cost-benefit ratio is favorable. Identification of which patient populations are at highest risk for synchronous bilateral breast cancer and who would benefit most needs to be investigated. Currently, screening MR imaging in patients with risk factors for bilateral cancer is not recommended outside the research setting. Other modalities including US and digital mammography are being investigated as methods for screening high-risk patients. Other avenues for further investigation include determination of the sensitivity and specificity of screening MR imaging in a large population. Findings of a prospective study in which mammography is compared with MR imaging in breast cancer detection should offer additional insights.
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FOOTNOTES |
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Author contributions: Guarantors of integrity of entire study, S.G.L., S.G.O.; study concepts, S.G.L., S.G.O., M.D.S.; study design, S.G.L., S.G.O., M.D.S., I.J.W., E.C.J.; literature research, S.G.L., S.G.O., E.C.J.; clinical studies, all authors; data acquisition, S.G.L., S.G.O., M.D.S.; data analysis/interpretation, S.G.L., S.G.O., M.D.S., I.J.W., E.C.J.; statistical analysis, M.E.P., S.G.L., S.G.O., I.J.W., E.C.J.; manuscript preparation and definition of intellectual content, S.G.L., S.G.O., I.J.W., E.C.J., M.D.S.; manuscript editing, M.E.P., S.G.L., S.G.O.; manuscript revision/review and final version approval, all authors.
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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